Gastric and small intestinal organoids differentiated from human pluripotent stem cells (hPSCs) have revolutionized the study of gastrointestinal development and disease. Distal gut tissues such as cecum and colon, however, have proved considerably more challenging to derive in vitro. Here we report the differentiation of human colonic organoids (HCOs) from hPSCs. We found that BMP signaling is required to establish a posterior SATB2+ domain in developing and postnatal intestinal epithelium. Brief activation of BMP signaling is sufficient to activate a posterior HOX code and direct hPSC-derived gut tube cultures into HCOs. In vitro, HCOs express colonic markers and contained colon-specific cell populations. Following transplantation into mice, HCOs undergo morphogenesis and maturation to form tissue that exhibits molecular, cellular, and morphologic properties of human colon. Together these data show BMP-dependent patterning of human hindgut into HCOs, which will be valuable for studying diseases including colitis and colon cancer.

中文翻译：

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通过瞬时激活 BMP 信号将人类多能干细胞分化为结肠类器官。

从人类多能干细胞 (hPSC) 分化而来的胃和小肠类器官彻底改变了胃肠道发育和疾病的研究。然而，远端肠道组织，如盲肠和结肠，已证明在体外获得相当具有挑战性。在这里，我们报告了人类结肠类器官 (HCO) 与 hPSC 的分化。我们发现 BMP 信号需要在发育中和出生后的肠上皮细胞中建立后 SATB2+ 结构域。BMP 信号的短暂激活足以激活后部 HOX 代码并将 hPSC 衍生的肠管培养物引导至 HCO。在体外，HCO 表达结肠标记物并包含结肠特异性细胞群。移植到小鼠体内后，HCO 经历形态发生和成熟，形成具有分子、细胞、和人类结肠的形态特征。这些数据共同显示了人类后肠进入 HCO 的 BMP 依赖性模式，这对于研究包括结肠炎和结肠癌在内的疾病很有价值。